Microtubules are a topic of intense research because of their important and multiple functions in the cell. Many of the potential anticancer agents act on microtubules and arrest mitosis as during mitotic cell division, microtubules play a crucial role by maintaining proper spindle function. Microtubule effectors work in two ways, they can interfere with microtubule dynamics and they can shift the tubulin-microtubule equilibrium in the cell by either inducing or inhibiting microtubule polymerization. There are three major classes of microtubule effectors. Taxanes stabilize microtubules by blocking disassembly. Vinca alkaloids and colchicine site binders destabilize microtubules by the inhibition of assembly of tubulin molecules, the major component of microtubules. Taxanes like Paclitaxel, docetaxel and vinca alkaloids like vincristine and vinblastine are well characterized and widely used clinically in different types of malignancies.
The main drawback of Taxanes and vinca alkaloids is that their use is limited by the development of drug resistance, neurotoxicity and limited availability leading to very high expenses involved.
The derivatives of diaminoketothiazoles have received much attention lately as inhibitors of cyclin-dependent kinases and glycogen synthase kinase-3. These are thus claimed to be useful Sir fee treatment of malignancies and Alzhemer's disease, impaired glucose tolerance, Type 1 and 2 diabetes.
For the synthesis of diaminoketothiazole, there exists only few methods. The first method makes use of a cyanothiourea derivative to provide the (C-N-C-S) atoms required for the thiazole construction and the remaining C atom is sourced from an alpha-haloketone. The second method utilizes thiocarbamoylamidine derivatives as fee source of the (C-N-C-S) four-atom complement
In the third approach, an S-alkyldithiobiuret serves as synthon for providing the (C-N-C-S) four-atom complement. These methods are usually suited for the solution phase synthesis of the title compounds. However, in the light of combinatorial library synthesis, solid phase methods are much more desirable. Such approaches allow rapid synthesis of a large number of analogue molecules that can be later subjected to bioactivity screening.